The objectives of this project are to delineate the cellular site(s) and mechanisms of action of ethanol in mammalian brain in an effort to understand what CNS changes may underlie the effects of chronic alcohol exposure. We have initiated our study of drug effects at the level of the cerebella Purkinje cells in rats. 1) Acute, peripherally administered Ethanol has an acute, possibly indirect, activating effect on the spontaneous firing of these neurons. Chronic Ethanol treatment (by gavage sufficient to produce blood levels of 100-300 mg/dl) and acute withdrawal results in a significant reduction in Purkinje cell firing and with decreased frequency of climbing fiber dicharges. In order to provide a pharmacological comparison of these effects of Ethanol, we also explored under similar experimental conditions the effects of chronic treatment with the tricyclic anti-depressant desmethylimipramine and with Li. Single acute doses of DMI or Li also slow Purkinje cell firing. Purkinje cell firing patterns may provide a sensitive index to the site and mechanisms of adaptation to chronic Ethanol exposure.